The research program is to continue studies on insulin secretion by the beta cell with a particular emphasis on the initiation of release of insulin from the beta cell following glucose stimulation. The in vitro perifusion system for the maintenance of isolated islets in vitro will continue to be used to study the mechanism of alloxan inhibition of glucose-induced insulin release in vitro and the protective effect of hexoses and other agents against this inhibitory action of alloxan. Studies on the effect of alloxan on hexose transport in the isolated rat islets are in progress. Monolayer cultures of adult rat islets are used for studies on the intracellular movement of beta granules by cinephotomicroscopy correlated with insulin release from these cells by various agents. Studies on the in vivo function of isolated islets transplanted into the liver by portal vein injection in experimental diabetic rats of the Lewis strain will be accomplished. These studies will assess the function of the transplanted islets with respect to the pattern of the glucose tolerance test in regards to glucose, insulin, and glucagon levels. In vitro studies on insulin and glucagon secretion of transplanted islets isolated from the liver will be attempted. Studies will be continued on the development of techniques for the mass isolation of normal human islets for subsequent in vitro studies on insulin formation, storage, and release. Studies will be continued on the role of the microtubular system in the intracellular transport of beta granules and the primary site of action of cytochalasin B on the beta cell.